The potential role of antiretroviral therapy (ART) for HIV-1 prevention - specifically treatment of HIV-1 infected persons to decrease their infectiousness and pre-exposure prophylaxis (PrEP) for HIV-1 uninfected persons to prevent acquisition - is a topic of significant public health interest. There is great scientific enthusiasm that earlier initiation of ART as treatment (i.e., at high CD4 counts, earlier than current treatment guidelines) and PrEP may prove to be highly efficacious strategies for prevention of HIV-1, and both approaches are being evaluated in clinical trials worldwide. Critical unanswered delivery questions for ART- based HIV-1 prevention include whether HIV-1 infected persons would accept earlier ART use to reduce their risk for transmitting HIV-1 and high-risk HIV-1 negative persons would use PrEP, whether concerns about side effects of early ART or PrEP would discourage long-term use, and whether self-perceived HIV-1 risk and fertility intention can be used to identify higher-risk subgroups for delivery, including intermittent or coitally- based PrEP to permit safer conception. Stable, heterosexual, African HIV-1 serodiscordant couples (i.e., in which one member is HIV-1 infected and the other uninfected) face high risk of HIV-1 transmission. Efficacy trials of ART for HIV-1 prevention and PrEP will be completed in the next 2-3 years, and if demonstrated to prevent HIV-1, serodiscordant couples will be a prime target for ART-based prevention. We are conducting a placebo-controlled clinical trial of tenofovir-based PrEP among 4700 HIV-1 serodiscordant couples in Kenya and Uganda (the Partners PrEP Study), which will be completed in 2012. This cohort of HIV-1 serodiscordant couples is an ideal population for exploring critical questions about ART-based prevention, as both members have been counseled extensively on ART and the concept of PrEP, HIV-1 uninfected partners have been exposed to potential side effects of PrEP, and HIV-1 infected partners receive ongoing clinical care including referral for ART when eligible by national guidelines. We propose to evaluate user preferences and risk-based targeting of ART-based HIV-1 prevention in a nested study among Partners PrEP Study participants at the Thika, Kenya site (N=~500 couples), using quantitative and qualitative methodologies. The project team has the expertise and experience to complete the proposed multidisciplinary work. We will: 1) determine user perceptions of ART-based HIV-1 prevention in HIV-1 discordant couples, including interest in, perceived benefits of, and concerns about early ART initiation for HIV-1 prevention in HIV-1 infected persons and interest in, tolerance of side effects, willingness to pay, and potential long-term use of PrEP by HIV-1 uninfected persons in HIV-1 serodiscordant partnerships, 2) assess whether self-perceived HIV-1 risk and fertility intentions among African HIV-1 serodiscordant couples correlate with HIV-1 risk behaviors, and could be used to target ART-based prevention implementation, and 3) prospectively measure sexual behavior, risk perception and fertility planning, and PrEP use, using cell phone data collection, providing a real-time, ecologic assessment of sexual risk and prevention behaviors. The proposed project offers an unprecedented opportunity to explore the critical public health questions surrounding ART-based HIV-1 prevention in a target population for implementation. The project is novel and significant in its integration of biobehavioral and sociocultural research, focus on primary HIV-1 prevention and prevention of transmission from persons with HIV-1, target of dyads to identify appropriate prevention approaches, and aim to identify barriers and facilitators for dissemination of effective HIV-1 prevention. PUBLIC HEALTH RELEVANCE: Antiretroviral therapy (ART), used as treatment of HIV-1 infected persons to decrease their infectiousness and as pre-exposure prophylaxis (PrEP) for HIV-1 uninfected persons, has been proposed as potentially highly effective for HIV-1 prevention. There are many unanswered questions about how to implement preventive ART for HIV-1 infected persons and PrEP for high-risk HIV-1 uninfected persons (if efficacious in trials) as complementary HIV-1 prevention strategies. Stable, heterosexual, African HIV-1 serodiscordant couples (i.e., in which one member is HIV-1 infected and the other uninfected) face high risk of HIV-1 transmission and are a priority for ART-based HIV-1 prevention. We propose to evaluate user preferences and risk-based targeting of ART-based HIV-1 prevention among HIV-1 serodiscordant couples in Thika, Kenya.